Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIX22S)

• DOT Name: Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2)
• Synonyms: EC 1.-.-.-
• Gene Name: PYROXD2
• Related Disease:
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Clear cell renal carcinoma
  Esophageal squamous cell carcinoma
  Narcolepsy
  Renal cell carcinoma
  Acute myelogenous leukaemia
  Advanced cancer
• UniProt ID: PYRD2_HUMAN
• EC Number: 1.-.-.-
• Pfam ID: PF01593 ; PF13450
• Sequence:
  MAASGRGLCKAVAASPFPAWRRDNTEARGGLKPEYDAVVIGAGHNGLVAAAYLQRLGVNT
  AVFERRHVIGGAAVTEEIIPGFKFSRASYLLSLLRPQIYTDLELKKHGLRLHLRNPYSFT
  PMLEEGAGSKVPRCLLLGTDMAENQKQIAQFSQKDAQVFPKYEEFMHRLALAIDPLLDAA
  PVDMAAFQHGSLLQRMRSLSTLKPLLKAGRILGAQLPRYYEVLTAPITKVLDQWFESEPL
  KATLATDAVIGAMTSPHTPGSGYVLLHHVMGGLEGMQGAWGYVQGGMGALSDAIASSATT
  HGASIFTEKTVAKVQVNSEGCVQGVVLEDGTEVRSKMVLSNTSPQITFLKLTPQEWLPEE
  FLERISQLDTRSPVTKINVAVDRLPSFLAAPNAPRGQPLPHHQCSIHLNCEDTLLLHQAF
  EDAMDGLPSHRPVIELCIPSSLDPTLAPPGCHVVSLFTQYMPYTLAGGKAWDEQERDAYA
  DRVFDCIEVYAPGFKDSVVGRDILTPPDLERIFGLPGGNIFHCAMSLDQLYFARPVPLHS
  GYRCPLQGLYLCGSGAHPGGGVMGAAGRNAAHVAFRDLKSM
• Function: Probable oxidoreductase that may play a role as regulator of mitochondrial function.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[3]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Disputed	Altered Expression	[6]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[18]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[15]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 2 (PYROXD2).	[17]

References

• [1] Pyridine nucleotide-disulphide oxidoreductase domain 2 (PYROXD2): Role in mitochondrial function.Mitochondrion. 2019 Jul;47:114-124. doi: 10.1016/j.mito.2019.05.007. Epub 2019 Jun 3.
• [2] YueF overexpression inhibits cell proliferation partly through p21 upregulation in renal cell carcinoma.Int J Mol Sci. 2011;12(4):2477-87. doi: 10.3390/ijms12042477. Epub 2011 Apr 11.
• [3] A Novel Clinical Six-Flavoprotein-Gene Signature Predicts Prognosis in Esophageal Squamous Cell Carcinoma.Biomed Res Int. 2019 Oct 30;2019:3869825. doi: 10.1155/2019/3869825. eCollection 2019.
• [4] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [5] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [6] Myeloid zinc finger 1 protein is a key transcription stimulating factor of PYROXD2 promoter.Oncol Rep. 2017 Nov;38(5):3245-3253. doi: 10.3892/or.2017.5990. Epub 2017 Sep 22.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [16] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.